Suzuki Tomoto, Takakubo Yuya, Oki Hiroharu, Liu Xing, Honma Ryusuke, Naganuma Yasushi, Goodman Stuart B, Kaneko Mika K, Kato Yukinari, Takagi Michiaki
1 Department of Orthopaedic Surgery, Faculty of Medicine, Yamagata University , Yamagata, Japan .
2 Department of Orthopaedic Surgery, Stanford University , Stanford, California.
Monoclon Antib Immunodiagn Immunother. 2018 Feb;37(1):12-19. doi: 10.1089/mab.2017.0047. Epub 2018 Jan 29.
Podoplanin (PDPN) is a transmembrane sialoglycoprotein, which is expressed in several normal tissues and malignant tumors. Although PDPN expression in rheumatoid arthritis (RA) has been reported, the role of PDPN in RA and other arthritic conditions has not been fully elucidated. In this study, we examined PDPN expression in inflammatory synovial tissues using an anti-human PDPN (hPDPN) monoclonal antibody (mAb) panel to select the most useful one for evaluation of synovitis. Synovial tissue samples were obtained from 11 RA patients and 9 osteoarthritis (OA) patients undergoing joint surgery. PDPN-positive cells were immunostained by a panel of PDPN mAbs (NZ-1, LpMab-3, LpMab-7, LpMab-10, LpMab-12, LpMab-13, and LpMab-17), followed by cell grading of inflammation and cell counting of PDPN-positivity by a quantitative analyzer. Immunohistochemistry showed that PDPN was markedly expressed in both macrophage-like type A and fibroblast-like type B lining cells of the hyperplastic synovial lining cell layer, and macrophages and fibroblasts in the stroma of RA. Among anti-PDPN mAbs, LpMab-12 showed the highest score. In inflammatory OA synovium, PDPN expression was also detectable. Although LpMab-12 also showed the highest score in OA, the difference was not statistically significant. The inflammatory synovitis score of RA was significantly higher than that of OA. PDPN was expressed in inflammatory lining cells and sublining stroma of RA and OA synovium. In the seven anti-hPDPN antibodies examined, LpMab-12 was the most stainable antibody for PDPN in RA synovitis. Thus, LpMab-12 for PDPN has a possible and promising specific biomarker for evaluating synovitis in RA and inflammatory OA.
血小板源性内皮细胞黏附分子（PDPN）是一种跨膜唾液酸糖蛋白，在多种正常组织和恶性肿瘤中均有表达。尽管已有关于类风湿关节炎（RA）中PDPN表达的报道，但PDPN在RA及其他关节炎病症中的作用尚未完全阐明。在本研究中，我们使用抗人PDPN（hPDPN）单克隆抗体（mAb）组检测炎症滑膜组织中PDPN的表达，以选择最有助于评估滑膜炎的抗体。滑膜组织样本取自11例接受关节手术的RA患者和9例骨关节炎（OA）患者。用一组PDPN mAb（NZ-1、LpMab-3、LpMab-7、LpMab-10、LpMab-12、LpMab-13和LpMab-17）对PDPN阳性细胞进行免疫染色，随后通过定量分析仪对炎症进行细胞分级并对PDPN阳性进行细胞计数。免疫组织化学显示，PDPN在增生性滑膜衬里细胞层的巨噬细胞样A型和成纤维细胞样B型衬里细胞以及RA基质中的巨噬细胞和成纤维细胞中均有明显表达。在抗PDPN mAb中，LpMab-12得分最高。在炎症性OA滑膜中，也可检测到PDPN表达。尽管LpMab-12在OA中得分也最高，但差异无统计学意义。RA的炎症滑膜炎评分显著高于OA。PDPN在RA和OA滑膜的炎症衬里细胞及衬里下层基质中均有表达。在所检测的七种抗hPDPN抗体中，LpMab-12是RA滑膜炎中对PDPN染色性最强的抗体。因此，针对PDPN的LpMab-12可能是评估RA和炎症性OA滑膜炎的一种有前景的特异性生物标志物。
